Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis
Abstract Background Natural killer (NK) cells hold great promise in treating diverse hematopoietic and solid tumors. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells offer an 'off-the-shelf' solution. Hematopoietic stem and progenitor cells (HSPCs...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03461-x |
| _version_ | 1827635394200469504 |
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| author | Wei Wen Xiang Chen Xin-Yi Shen Hua-Yu Li Feng Zhang Feng-Qi Fang Xiao-Bing Zhang |
| author_facet | Wei Wen Xiang Chen Xin-Yi Shen Hua-Yu Li Feng Zhang Feng-Qi Fang Xiao-Bing Zhang |
| author_sort | Wei Wen |
| collection | DOAJ |
| description | Abstract Background Natural killer (NK) cells hold great promise in treating diverse hematopoietic and solid tumors. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells offer an 'off-the-shelf' solution. Hematopoietic stem and progenitor cells (HSPCs) derived from cord blood pose no risk to the newborn or mother and are virtually ideal sources for NK cell differentiation. Methods We developed a modified protocol to differentiate HSPCs to NK cells under serum-free conditions using defined factors. The HSPC-derived NK (HSC-NK) cells could be expanded in a K562 feeder cell-dependent manner. Furthermore, using lentivirus transduction, chimeric antigen receptor (CAR)-modified HSPCs could be differentiated into NK cells, leading to the establishment of CAR-NK cells. Results The efficiency of NK cell differentiation from HSPCs was increased through the simple modulation of osmotic pressure by the addition of sodium chloride or glucose. Furthermore, the hyperosmosis-primed HSC-NK cells exhibited enhanced proliferation capacity and maintained normal functional characteristics, including transcriptome and antitumor efficacy. The optimized protocol yielded approximately 1.8 million NK cells from a single CD34-positive cell within a 28-day cycle, which signifies more than a ten-fold increase in efficiency relative to the conventional methods. This optimized protocol was also suitable for generating CAR-NK cells with high yields compared to standard conditions. Conclusions The results of this study establish high osmotic pressure as a simple yet powerful adjustment that significantly enhances the efficiency and functionality of HSC-NK cells, including CAR-NK cells. This optimized protocol could lead to cost-effective, high-yield NK cell therapies, potentially revolutionizing cancer immunotherapy strategies. |
| first_indexed | 2024-03-09T15:26:11Z |
| format | Article |
| id | doaj.art-447de0e7b36f4117b5a463443db1dadc |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-09T15:26:11Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-447de0e7b36f4117b5a463443db1dadc2023-11-26T12:30:46ZengBMCStem Cell Research & Therapy1757-65122023-10-0114111410.1186/s13287-023-03461-xEnhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosisWei Wen0Xiang Chen1Xin-Yi Shen2Hua-Yu Li3Feng Zhang4Feng-Qi Fang5Xiao-Bing Zhang6State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Oncology, The First Affiliated Hospital of Dalian Medical UniversityCollege of Computer Science and Technology, China University of Petroleum (East China)College of Computer Science and Technology, China University of Petroleum (East China)State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Oncology, The First Affiliated Hospital of Dalian Medical UniversityState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Natural killer (NK) cells hold great promise in treating diverse hematopoietic and solid tumors. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells offer an 'off-the-shelf' solution. Hematopoietic stem and progenitor cells (HSPCs) derived from cord blood pose no risk to the newborn or mother and are virtually ideal sources for NK cell differentiation. Methods We developed a modified protocol to differentiate HSPCs to NK cells under serum-free conditions using defined factors. The HSPC-derived NK (HSC-NK) cells could be expanded in a K562 feeder cell-dependent manner. Furthermore, using lentivirus transduction, chimeric antigen receptor (CAR)-modified HSPCs could be differentiated into NK cells, leading to the establishment of CAR-NK cells. Results The efficiency of NK cell differentiation from HSPCs was increased through the simple modulation of osmotic pressure by the addition of sodium chloride or glucose. Furthermore, the hyperosmosis-primed HSC-NK cells exhibited enhanced proliferation capacity and maintained normal functional characteristics, including transcriptome and antitumor efficacy. The optimized protocol yielded approximately 1.8 million NK cells from a single CD34-positive cell within a 28-day cycle, which signifies more than a ten-fold increase in efficiency relative to the conventional methods. This optimized protocol was also suitable for generating CAR-NK cells with high yields compared to standard conditions. Conclusions The results of this study establish high osmotic pressure as a simple yet powerful adjustment that significantly enhances the efficiency and functionality of HSC-NK cells, including CAR-NK cells. This optimized protocol could lead to cost-effective, high-yield NK cell therapies, potentially revolutionizing cancer immunotherapy strategies.https://doi.org/10.1186/s13287-023-03461-xNatural killer (NK) cellsHematopoietic stem and progenitor cells (HSPCs)DifferentiationHyperosmosisImmunotherapy |
| spellingShingle | Wei Wen Xiang Chen Xin-Yi Shen Hua-Yu Li Feng Zhang Feng-Qi Fang Xiao-Bing Zhang Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis Stem Cell Research & Therapy Natural killer (NK) cells Hematopoietic stem and progenitor cells (HSPCs) Differentiation Hyperosmosis Immunotherapy |
| title | Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis |
| title_full | Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis |
| title_fullStr | Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis |
| title_full_unstemmed | Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis |
| title_short | Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis |
| title_sort | enhancing cord blood stem cell derived nk cell growth and differentiation through hyperosmosis |
| topic | Natural killer (NK) cells Hematopoietic stem and progenitor cells (HSPCs) Differentiation Hyperosmosis Immunotherapy |
| url | https://doi.org/10.1186/s13287-023-03461-x |
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